Hemispheric asymmetry in ocean change and the productivity of ecosystem sentinels.

Climate change and other human activities are causing profound effects on marine ecosystem productivity. We show that the breeding success of seabirds is tracking hemispheric differences in ocean warming and human impacts, with the strongest effects on fish-eating, surface-foraging species in the north. Hemispheric asymmetry suggests the need for ocean management at hemispheric scales. For the north, tactical, climate-based recovery plans for forage fish resources are needed to recover seabird breeding productivity. In the south, lower-magnitude change in seabird productivity presents opportunities for strategic management approaches such as large marine protected areas to sustain food webs and maintain predator productivity. Global monitoring of seabird productivity enables the detection of ecosystem change in remote regions and contributes to our understanding of marine climate impacts on ecosystems.

An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis.

Composition of the gut microbiota has profound effects on intestinal carcinogenesis. Diet and host genetics play critical roles in shaping the composition of gut microbiota. Whether diet and host genes interact with each other to bring specific changes in gut microbiota that affect intestinal carcinogenesis is unknown. Ability of dietary fibre to specifically increase beneficial gut microbiota at the expense of pathogenic bacteria in vivo via unknown mechanism is an important process that suppresses intestinal inflammation and carcinogenesis. Free fatty acid receptor 2 (FFAR2 or GPR43) is a receptor for short-chain fatty acids (acetate, propionate and butyrate), metabolites of dietary fibre fermentation by gut microbiota. Here, we show FFAR2 is down modulated in human colon cancers than matched adjacent healthy tissue. Consistent with this, Ffar2(-/-) mice are hypersusceptible to development of intestinal carcinogenesis. Dietary fibre suppressed colon carcinogenesis in an Ffar2-dependent manner. Ffar2 played an essential role in dietary fibre-mediated promotion of beneficial gut microbiota, Bifidobacterium species (spp) and suppression of Helicobacter hepaticus and Prevotellaceae. Moreover, numbers of Bifidobacterium is reduced, whereas those of Prevotellaceae are increased in human colon cancers than matched adjacent normal tissue. Administration of Bifidobacterium mitigated intestinal inflammation and carcinogenesis in Ffar2(-/-) mice. Taken together, these findings suggest that interplay between dietary fibre and Ffar2 play a key role in promoting healthy composition of gut microbiota that stimulates intestinal health.

Ictal infraslow activity in stereoelectroencephalography: Beyond the "DC shift".

OBJECTIVES: The significance of infraslow activity (ISA) in focal epilepsies is largely unknown. Recent work has demonstrated ictal ISA to be more widespread in expression than originally understood. Analysis of ISA by stereoelectroencephalography (SEEG) may help to clarify its localizing value, namely the focal versus widespread expression of ISA. METHODS: The ictal SEEG records for fifteen consecutive adult patients were retrospectively analyzed, using both conventional (1.6-70 Hz) and infraslow (0.01-0.1 Hz) bandpass filters. When justified, seizures were averaged in the infraslow band to clarify their stereotypy. Wavelets were used to quantify the time-frequency characteristics of ISA. RESULTS: All clinical seizures were found to possess ISA, and this was markedly invariant across seizures in a given patient. ISA showed biphasic peaks in power, both at ictal onset and offset, with this most prominent in the anatomical structures implicated by conventional analysis. In addition, ISA demonstrated an association with low voltage fast activity, and possessed a more restricted field than conventional activity. CONCLUSIONS: ISA is both widespread (anatomically distributed) and focal (closed electric field). Seizures possess an infraslow spatiotemporal signature. SIGNIFICANCE: Beyond representing a "focus" of paroxysmal activity, ISA must arise from a network process as a component of wideband ictal dynamics. How this relates to clinical definition of the epileptogenic zone requires further study.

Self-assembly of gold supraparticles with crystallographically aligned and strongly coupled nanoparticle building blocks for SERS and photothermal therapy.

A new method is introduced for self-assembling citrate-capped gold nanoparticles into supraparticles with crystallographically aligned building blocks. It consists in confining gld nanoparticles inside a cellulose acetate membrane. The constituent nanoparticles are in close contact in the superstructure, and therefore generate hot spots leading to intense Surface-Enhanced Raman Scattering (SERS) signals. They also generate more plasmonic heat than the nanoparticle building blocks. The supraparticles are internalized by cells and show low cytotoxicity, but can kill cancer cells when irradiated with a laser. This, along with the improved plasmonic properties arising from their assembly, makes the gold supraparticles promising materials for applications in bioimaging and nanomedicine.

Climate change. Climate change and wind intensification in coastal upwelling ecosystems.

In 1990, Andrew Bakun proposed that increasing greenhouse gas concentrations would force intensification of upwelling-favorable winds in eastern boundary current systems that contribute substantial services to society. Because there is considerable disagreement about whether contemporary wind trends support Bakun's hypothesis, we performed a meta-analysis of the literature on upwelling-favorable wind intensification. The preponderance of published analyses suggests that winds have intensified in the California, Benguela, and Humboldt upwelling systems and weakened in the Iberian system over time scales ranging up to 60 years; wind change is equivocal in the Canary system. Stronger intensification signals are observed at higher latitudes, consistent with the warming pattern associated with climate change. Overall, reported changes in coastal winds, although subtle and spatially variable, support Bakun's hypothesis of upwelling intensification in eastern boundary current systems.

Guidance for the core content of a Curriculum in Special Care Dentistry at the undergraduate level.

Given the rapidly changing demography of populations worldwide, dental professionals of the future need to be able to meet the challenge posed by the evolving landscape in health care needs. Leading institutions are now embedding teaching and learning in special care dentistry (SCD) within their curricula, to provide students with the knowledge, skills and attitudes to meet the oral health needs of vulnerable groups within their communities. The International Association for Disability and Oral Health (iADH) has initiated the development of undergraduate curriculum guidance in SCD through a consensus process. The curriculum in SCD is defined in statements of learning outcomes with many of the skills being transferable across the undergraduate course. This curriculum includes examples of teaching and assessment, designed to enhance critical thinking in relation to SCD and to promote positive attitudes towards disability and diversity. The learning outcomes are designed to be readily adapted to conform to the generic profiles and competencies, already identified in undergraduate frameworks by global educational associations, as well as meeting the requirements of professional regulatory bodies worldwide. Suggestions for teaching and learning are not intended to be prescriptive; rather, they act as a signpost to possible routes to student learning. Ideally, this will require that students have a sufficiently diverse patient case mix during their undergraduate studies, to achieve the required levels of confidence and competence by the time they graduate. Clinical care competencies in SCD emphasise the need for learners to broaden their theoretical knowledge and understanding through practical experience in providing care for people with special health care needs. It is crucial to the development of equitable dental services for all members of a community, that these learning outcomes are embedded into evolving curricula but most importantly, that they are evaluated and refined in a dynamic way with shared learning for all teachers.

Intranasal/intravenous sedation for the dental care of adults with severe disabilities: a multicentre prospective audit.

OBJECTIVE: This study was designed to provide an evaluation of the combined intranasal/intravenous midazolam sedation technique. It involved adults with severe disabilities which prevented them from being able to co-operate with dental treatment and intravenous cannulation for sedation. METHOD: Following a previous retrospective audit, additional treatment centres were enrolled and a standardised form used to collect prospective data about the effectiveness of the technique in facilitating cannulation, dental examination and treatment. Data was also collected on safety and patient acceptability. RESULTS: In a total of 316 sedation episodes in primary and secondary care settings, cannulation was achieved in 96.2% (304). Dental examination and treatment was able to be carried out without major interference from the patient in 78.8% (241) episodes. Adverse sedation events occurred in 6.0% (19), the most frequent being desaturation which was easily managed. There were no incidents with serious sequelae. Favourable acceptability ratings were given by carers regarding advantages of ease of administration and speed of onset of the intranasal dose, plus reduction in the stress associated with cannulation and treatment. CONCLUSIONS: This study provides further evidence to support the effectiveness, safety and acceptability of this technique. The authors suggest this provides sufficient basis to justify its use by suitably trained dental practitioners in primary care as part of the spectrum of anxiety and behaviour management for this group.

Novel anti-idiotype antibody therapy for lipooligosaccharide-induced experimental autoimmune neuritis: use relevant to Guillain-Barré syndrome.

Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C.jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies.

Retrospective audit of the efficacy and safety of the combined intranasal/intravenous midazolam sedation technique for the dental treatment of adults with learning disability.

INTRODUCTION: The provision of dental care for adults with severe learning disability presents problems. The approach to treatment has often been provided under general anaesthesia tending to result in exodontia rather than restorative care. This paper presents an alternative to this option using conscious sedation. METHODS: A multi-centred retrospective audit was reported on using data from Canterbury, Warwick, Dorset and Cardiff. Patients included adults with varying degrees of disability for whom treatment using local anaesthesia, inhalation sedation, and the acceptance of intravenous cannulation was not possible. Sedation was provided by midazolam first administered by the intranasal followed by the intravenous route. RESULTS: From a total of 222 episodes of sedation 128 (57.65%) accepted treatment well and 75 (33.78%) presented slight problems which did not compromise treatment. In 19 cases (8.55%) treatment with sedation was not possible and a referral was made for general anaesthesia. CONCLUSIONS: Results showed that a range of different treatments were carried out including advanced restorative care. This paper proposes that the technique described is safe and effective in providing a good standard of dental care for adults with severe learning disability.

Relapsing encephalopathy in a patient with alpha-methylacyl-CoA racemase deficiency.

Alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies.

Cardiac risk factors for dental procedures: knowledge among dental practitioners in Wales.

OBJECTIVES: To determine knowledge and educational needs of dental practitioners in Wales regarding congenital or acquired cardiac disease and the provision of antibiotic prophylaxis. DESIGN: Self-administered postal questionnaire. SETTINGS: Cardiff University Dental Hospital, district general hospitals (HDS), all general dental practices (GDP) and community dental service (CDS) clinics throughout Wales. Methods A questionnaire sent to 1,182 dentists in Wales in 2004-5. RESULTS: 528 questionnaires were returned (a response rate of 45%). These were analysed using one-way analysis of variance to compare summary scores between the occupation groups. Significant differences in knowledge of cardiac risk factors for infective endocarditis and for dental procedures requiring cover were observed between the occupation groups. The majority of dentists (92% GDPs, 94% CDS and 77% HDS) requested postgraduate education in cardiac risk factors and laminated flow diagrams for their surgeries as the preferred educational format. CONCLUSION: The knowledge of Welsh dentists regarding cardiac conditions or procedures which are risk factors for paediatric and adult patients varied according to place of work. The study identified potential for under- and over-prescription of antibiotic prophylaxis within the current guidance. There was confusion as to which patient groups and cardiac conditions required prophylaxis and for which particular dental procedures. Postgraduate education detailing advances in cardiology practice is necessary for dentists.

Acetylcholine neuroprotection against glutamate-induced excitotoxicity in adult pig retinal ganglion cells is partially mediated through alpha4 nAChRs.

In the mammalian retina, excess glutamate release has been shown to be involved in retinal ganglion cell (RGC) death associated with various diseases. Recent studies have determined that activation of alpha7 nicotinic acetylcholine receptors (nAChRs) partially protect isolated RGCs from glutamate-induced excitotoxicity. In this study, we further classify the types of nAChRs involved in neuroprotection against glutamate-induced excitotoxicity using isolated adult pig RGCs. Cells were isolated with a modified two-step immunoselective panning technique designed to isolate RGCs from other retinal neurons. Once isolated, nAChR subunits were identified using a combination of pharmacological and immunocytochemical techniques. In cell culture experiments, a variety of alpha4 nAChR specific agonists were found to have a partial neuroprotective against glutamate-induced excitotoxicity. This neuroprotection was abolished in the presence of the alpha4 nAChR antagonist, dihydro-beta-erythroidine (DHbetaE). Immunocytochemical results localized several nAChR subunits on isolated adult pig RGCs; in particular alpha4, alpha7 and beta2 nAChR subunits. Large RGCs exclusively immunostained with antibodies against alpha7 nAChR subunits whereas alpha4 and beta2 subunits exclusively immunostained only small RGCs. Double label experiments provided evidence that alpha4 and beta2 subunits co-localize on small RGCs. Knowledge of the receptor subtypes responsible for neuroprotection may lead to treatments associated with glutamate-induced excitotoxicity.

Pre-slaughter transport, AMP-activated protein kinase, glycolysis, and quality of pork loin.

Numerous studies have revealed that pre-slaughter stress, like transport, increases the occurrence of pale, soft, and exudative (PSE) pork meat. The molecular mechanism underlying this phenomenon, however, is poorly defined. In this study, we investigated the effects of pre-slaughter transport and subsequent rest on energy metabolism, AMP-activated protein kinase (AMPK) activation, and glycolysis in postmortem pork loin. Results indicated that pre-slaughter transport accelerated ATP depletion, which led to lower energy status in postmortem muscle immediately post-exsanguination when compared with control. The lower energy status led to AMPK activation within 1h postmortem, subsequently increasing glycolysis, leading to rapid glycolysis and high incidence of PSE meat. Allowing pigs to rest after transport restored energy status in muscle ante-mortem. Higher energy status then prevented premature and rapid AMPK activation in postmortem muscle and lessened the negative effects of pre-slaughter transport on meat quality. AMPK regulated glycolysis in postmortem muscle, at least partially, through phosphorylation and activation of phosphofructose kinase-2, since fructose-2,6-diphosphate content, an allosteric activator of phosphofructose kinase-1, was well correlated with AMPK activation and glycolytic rate. This suggests that AMPK is a potential molecular target for the control of PSE incidence in pork.

Episodic and semantic memory in mild cognitive impairment.

Little is known about episodic and semantic memory in the early predementia stage of Alzheimer's disease (AD), which is referred to as mild cognitive impairment (MCI). To explore person knowledge, item recognition and spatial associative memory, we designed the Face Place Test (FPT). A total of 75 subjects participated: 22 patients with early AD, 24 with MCI and 29 matched controls. As predicted, AD patients showed significant deficits in person naming, item recognition and recall of spatial location (placing). Surprisingly, subjects with MCI were also impaired on all components. There was no significant difference between AD and MCI except on the placing component. Analysis of the relationship between semantic (naming) and episodic (recognition and placing) components of the FPT revealed a significant association between the two episodic tasks, but not between episodic and semantic performance. Patients with MCI show deficits of episodic and semantic memory. The extent of impairment suggests dysfunction beyond the medial temporal lobe. The FPT might form the basis of a sensitive early indicator of AD.

Multidimensional measures of person knowledge and spatial associative learning: can these be applied to the differentiation of Alzheimer's disease from frontotemporal and vascular dementia?

Patients with early stage Alzheimer's disease (AD) show deficits in person knowledge and spatial associative memory. The current investigation examined the ability of impairment in these domains to differentiate AD from other overlapping conditions. In experiment 1, 14 AD patients, 21 vascular dementia (VaD) patients, 11 frontal variant frontotemporal dementia (fvFTD) patients and 41 controls were administered a graded faces test. VaD patients demonstrated a level of impairment comparable to the AD group on both the naming and person identification elements of the task. A mild naming deficit was revealed in the fvFTD group. In experiment 2, 22 AD patients, 23 patients with mild cognitive impairment (MCI), 11 fvFTD patients, 13 semantic dementia (SD) patients, and 23 elderly controls were administered the face-place test, a newly developed task that combines naming of famous faces, item recognition and spatial location. The naming component of the face-place test clearly differentiated SD patients from all dementia groups. All patient groups, except those with fvFTD, showed substantial deficits in the item recognition and spatial components. Consistency analyses indicated a fairly robust association between the two episodic components (item recognition and placing), but not between semantic and episodic elements of the FPT. Person knowledge deficits are, therefore, not specific to AD and the employment of face stimuli may influence the performance of SD patients on tasks of episodic memory.

Special Care Dentistry: attitudes of Specialists in Paediatric Dentistry practising in the UK to the creation of a new specialty.

OBJECTIVES: This study was designed to examine the attitudes of Specialists in Paediatric Dentistry (SPDs) practising in the UK towards the creation of a specialty of Special Care Dentistry (SCD). DESIGN: Data were collected by postal questionnaire. Sample and methods. Two hundred and eleven dentists whose names were entered on the General Dental Council's Specialist List in Paediatric Dentistry, and who were resident and practising in the UK, were asked to complete a questionnaire consisting of both open and closed questions. RESULTS: Questionnaires were returned by 167 (79.2%) of the eligible SPDs. One hundred and sixty respondents (95.8%) expressed an opinion in relation to the creation of a specialty of SCD. One hundred and forty-three respondents (85.6%) stated that they supported such a proposal. However, slightly fewer (n = 149) respondents were prepared to indicate what they considered to be the remit of the proposed specialty. Ninety-two respondents (55.1%) considered that it should be restricted to the provision of specialist care for adults with 'special needs'; the remaining 57 respondents felt that it should provide specialist care across the entire age spectrum. CONCLUSIONS: Among SPDs, there is overwhelming support for the creation of a specialty of SCD, the majority view being that this should be dedicated to the provision of specialist care for adults with 'special needs'.

Tissue factor and tissue factor pathway inhibitor.

The classical 'cascade/waterfall' hypothesis formulated to explain in vitro coagulation organised the amplification processes into the intrinsic and extrinsic pathways. Recent molecular biology and clinical data indicate that tissue factor/factor-VII interaction is the primary cellular initiator of coagulation in vivo. The process of blood coagulation is divided into an initiation phase followed by a propagation phase. The discovery of tissue factor pathway inhibitor further supports the revised theory of coagulation. Tissue factor is also a signalling receptor. Recent evidence has shown that blood-borne tissue factor has an important procoagulant function in sepsis, atherosclerosis and cancer, and other functions beyond haemostasis such as immune function and metastases.

Salicylidene salicylhydrazide, a selective inhibitor of beta 1-containing GABAA receptors.

1. A high-throughput assay utilizing the voltage/ion probe reader (VIPR) technology identified salicylidene salicylhydrazide (SCS) as being a potent selective inhibitor of alpha2beta1gamma1 GABA(A) receptors with a maximum inhibition of 56+/-5% and an IC(50) of 32 (23, 45) nm. 2. Evaluation of this compound using patch-clamp electrophysiological techniques demonstrated that the compound behaved in a manner selective for receptors containing the beta1 subunit (e.g. maximum inhibition of 68.1+/-2.7% and IC(50) value of 5.3 (4.4, 6.5) nm on alpha2beta1gamma1 receptors). The presence of a beta1 subunit was paramount for the inhibition with changes between alpha1 and alpha2, gamma1 and gamma2, and the presence of a subunit having little effect. 3. On all subtypes, SCS produced incomplete inhibition with the greatest level of inhibition at alpha1beta1gamma1 receptors (74.3+/-1.4%). SCS displayed no use or voltage dependence, suggesting that it does not bind within the channel region. Concentration - response curves to GABA in the presence of SCS revealed a reduction in the maximum response with no change in the EC(50) or Hill coefficient. In addition, SCS inhibited pentobarbitone-induced currents. 4. Threonine 255, located within transmembrane domain (TM) 1, and isoleucine 308, located extracellularly just prior to TM3, were required for inhibition by SCS. 5. SCS did not compete with the known allosteric modulators, picrotoxin, pregnenolone sulphate, dehydroepiandrosterone 3-sulphate, bicuculline, loreclezole or mefenamic acid. Neither was the inhibition by SCS influenced by the benzodiazepine site antagonist flumazenil. 6. In conclusion, SCS is unique in selectively inhibiting GABA(A) receptors containing the beta1 subunit via an allosteric mechanism. The importance of threonine 255 and isoleucine 308 within the beta1 subunit and the lack of interaction with a range of GABA(A) receptor modulators suggests that SCS is interacting at a previously unidentified site.